TABLE 2.
Summary of the roles HLA-C, E, F and G play in normal pregnancy and how their dysregulation contributes to preeclampsia.
| HLA Molecule | Role in Normal Pregnancy | Dysregulation in Preeclampsia |
|---|---|---|
| HLA-C | Expressed by EVTs | Some studies suggest that women with preeclampsia are more likely to have inhibitory KIR genotypes whereby interactions between HLA-C and KIR on NK cells fails to stimulate release of pro-migratory chemokines/cytokines and thus result in defective spiral artery remodeling |
| Presents pathogen-derived peptides to maternal T and NK cells and activates their cytotoxic responses for infection control | ||
| Interaction between HLA-C and KIRs stimulates NK cells to release chemokines and cytokines promoting trophoblast migration and spiral artery remodeling/physiologic conversion | ||
| HLA-E | Expressed by EVTs | Dysregulation/dysfunction in preeclampsia needs to be further investigated |
| Presents a limited set of viral pathogen-derived peptides to maternal T and NK cells and activates their cytotoxic responses for infection control | ||
| Protects trophoblasts from NK cell-mediated lysis via interactions with CD94/NKG2A receptors | ||
| HLA-F | Expressed by EVTs | Dysregulation/dysfunction in preeclampsia needs to be further investigated |
| Genetic variants causing reduced expression associated with decreased fertility, supporting as-yet undefined role in regulating NK cell activity at maternal-fetal interface | ||
| HLA-G | Expressed by both villous trophoblasts and EVTs | Decreased placental and circulating HLA-G levels are observed in preeclampsia and are associated with deficient spiral artery remodeling, decreased numbers of Tregs and increased expression of pro-inflammatory cytokines |
| Promotes maternal tolerance of the semi-allogenic fetus by inhibiting cytotoxic activity of maternal T and NK cells, and promoting the generation and persistence of Tregs | ||
| Promotes physiologic conversion/spiral artery remodeling by stimulating NK cells to release pro-migratory and proangiogenic chemokines and cytokines. Also interacts with endothelial cells via CD160 |